INTRODUCTION

The changes applied following the reorganization of the Emergency Deptment (ED) have had a considerable impact on the Stat Laboratories. In fact, the role of the ED is not anymore that of a simple sorting house towards the different departments or day hospital therapies. A new concept of critical patient stabilization has been introduced through diagnoses and therapies carried out with the maximum efficiency and timeliness (1). The labs have encountered some difficulties with these changes, accusing a significant increase in the workload, often interpreted as a deterioration of appropriateness. The truth is that the concept itself of an appropriate analysis request has changed a lot in comparison with the past. For this type of patients, the new mission is that of a more efficient and rapid treatment, following the hospital organization with the other clinical services. All of this in a moment where lab evolution is receiving strong pressure for cost cutting actions, causing lab operators disorientation, for both professionals and technicians, and hence the need for precise and detailed guidelines from the scientific societies. That was the aim on which the Study Group SiBioc has worked on “Emergency/Urgency Laboratory”.

MATERIALS AND METHODS

The main characteristic of work organisation, finalised to practical recommendations to be implemented on the field, is the classification of recommended test panels following the diagnostic path, that is referring to the accused symptoms and not on the clinical suspect cause, as it used to happen traditionally. The first evaluation carried out was to compare some diagnostics procedures applied throughout different labs in Italy. Together with some similar groups of tests requested in different hospitals, we also noticed a few differences caused by local procedures, on which we mostly concentrate our analysis of the scientific evidences. From the very beginning we got in contact with clinical experts of the two major scientific societies of this sector: Societa’ Italiana di Medicina di Emergenza ed Urgenza (Simeu – Italian Society of Emergency/Urgency Medicine) and the correspondent paediatric society (Simeup). The bibliographic research was centred on the main books written for Laboratory Medicine and Urgency Medicine (2-8), on the publications about the so-called “evidence-based medicine”(9-13) and on the “Pubmed” instrument of the “National Library of Medicine” (“National Institutes of Health”) (14), always using MeSH terminology that defines the different symptoms. Unfortunately studies that prove lab tests utility are very limited to some specific cases, while most of the common uses are based on traditional choices derived from clinical practices, limited studies and common known procedures. For these reasons, the collection of scientific evidences, and consequently the strength of the recommendation, could not reach a reasonable level of definition in several of the cases taken into consideration. Table 1 shows the adopted classification for these recommendations. The discussion on the following drafts on the present guidelines has remained open through the publication on the internet site made available by SIBioc. Particular attention has been paid to the modern organisation of the Accident & Emergency (A&E) and to its aims, that require a diagnostic competence and a range of tests much wider than in the past.

RESULTS

The final document produced at the end of this study is here explained. The clinical presentation pictures have been chosen among the most representative of the majority of real cases as observable in a common ED (table 2). For every section we present a short and introductive clinical picture, the diagnostic hypothesis to consider for the diagnosis or for the exclusion, a decisional algorithm based on clinical and laboratory criteria, the recommendation of certain exams to carry out and those appropriate for particular cases.

The guidelines here explained include only few of the typical presentation situations of A&E patients. They do not represent a systematic list, nor have a prescriptive value. They are however comprehensive of the most frequent situations or of those that more frequently require laboratory testing. This initiative is also meant to have a cultural and formative valence in order to help a good interaction between laboratory and clinic. As a matter of fact, lab counselling and urgency competence are both elements that can, and have to be developed through clinic cases discussion together with the application of guidelines that, otherwise, without an appropriate interaction and evaluation, would be of no effect.

CONSCIOUSNESS ALTERATION

Conscious state transitory disorders (named syncope if complete loss or lipothymia if incomplete) are a frequent case scenario in A&E. Persistent losses of consciousness range from coma to psychiatric disorders, with which they can get confused. They are usually examined with the “Glasgow coma scale”. Medical history is essential in the diagnosis and most of the time laboratory tests are not required. Lipothymia or syncope are often associated with various pathologies that will be presented in other chapters of this document, and that are studied for evidence of other symptoms and signs, e.g. heart attack, pulmonary embolism, dissection of the aorta, cardiac tamponade, infections. We will discuss here those situations in which a transitory or persistent alteration of the conscious state represents the main clinic element. The most important tests are aimed to recognizing a possible hypoglycaemia (that can manifest itself through different neurological symptoms), dehydration, hypovolemia or anaemia. Therefore the most common lab tests in this field are: glycaemia, electrolytes, urea and plasmatic creatinine, Complete Blood Count (CBC). These tests are appropriate only in the presence of a suspected hypovolemia or a metabolic disorder (grade C recommendation) (15-17). Toxicological tests could be requested if a specific suspect exists based on medical history. Without further and more specific signs, other tests or cardiac marker measurements are not recommended. Following table 3, most of the useful biochemical alterations can be identified. Lab tests have to be carried out before an eventual “coma cocktail” is to be administered (C grade). Troponine I determination, in case of a syncope, has been evaluated in a consistent case study, that has showed a dubious or inexistent benefit for the patient. It is therefore recommended only for more specific cardiac symptoms (B grade) (18). A classic mnemonic anagram is used not to forget any conditions that could alter the consciousness (TIPS-AEIOU-COMA), it could be useful to refer to the specific tests mentioned on table 4 (C grade). At this moment though the evaluation is not an initial one anymore but is in the stage of a diagnostic suspicion.

PARTICULAR CLINICAL CONDITIONS

SYNCOPE

Typical A&E situation is a short time consciousness loss, self-limiting (normally with fall on the floor), which requires an evaluation due to the mortality incidence of this condition of around 7.3% within a month. The “ROSE study” has recently identified as predictive factors 6 characteristics, 4 of which are laboratory tests (level II) (Table 5) (21). These results overturn previous appropriateness ideas in the use of indicated tests. These tests have to be applied when particular conditions can be excluded, like alcohol abuse, stroke, epileptic attack, hypoglycaemia, but when bradycardia is present.

COMA IN DIABETES MELLITUS

There are a number of potential reasons for coma in diabetics, both from cardiovascular or metabolic origin. The most common form is linked to hypoglycaemia depending upon an inadequate insulin administration. This event is easily detectable with the plasmatic glucose determination. Particular attention must be paid to the diagnosis of diabetic keto-acidosis and hyperosmolar coma, conditions that are both characterized by hyperglycaemia. In Table 6 are listed those tests considered useful to approach a diabetic patient with a consciousness alteration (22). An interpretation of this consciousness alteration in a hyperglycaemic patient could also be obtained by evaluating laboratory parameters listed on Table 7, as proposed by Kitabchi et al. (23).

ASTHENIA OR FATIGUE

Asthenia is one of the most vague symptoms due to its absolute subjectivity. The first 2 hypothesis to take into consideration are insomnia and depression. Notwithstanding the above, the patient has to be carefully evaluated because asthenia can be a symptom of an acute and serious pathology. A thorough medical history is fundamental and unavoidable in such cases before taking into consideration any laboratory test. When the symptom is a consequence of an organic pathology, the most common causes to consider are anaemia, kidney failure, diabetes and cardiac insufficiency (24, 25). Secondly, other causes can be hyperparathyroidism, thyroid conditions, rhabdomyolisis, surrenalic failure. Finally, there can be infectious (especially chronic ones), pharmacological and physiological causes. Recommended test are listed on Table 8 (C grade) (26). Based on clinical and first results evaluation, the decisional algorithm can proceed following the schemes reported in other chapters of these recommendations.

DIARRHOEA OR DIARRHOEA WITH VOMIT IN CHILD (ACUTE GASTROENTERITIS)

In most cases laboratory tests are unnecessary for these patients. The first evaluation is a clinical one and tends to classify the dehydration level in mild, moderate or acute, especially referring to capillary replenishment time, cutaneous turgor and respiratory deficiencies. Appropriate tests are recommended only in the following conditions:

-  Acute dehydration and/or shock

-  Moderate dehydration with discrepancy between clinical situation and degree of diarrhoea or vomit

-  Acute diarrhoea: discharge>10 ml/kg/hour

-  Age <3 months or body weight <4,5 kg

-  Sensory alteration

-  Parenteral hydration level

The convenient tests are listed on Table 9 (27).

Diagnostic usage of bicarbonates, ions and Osm with these patients has proved to be effective to a level II (B grade)(27). The exclusion of any dehydration presence could be obtained throughout serum bicarbonates evaluation (level II) to a cut-off of 17 mmol/L (negative feasibility ratio (LR)=0,22) or 15 (LR= 0,18) referring to a dehydration of 5%.

The aforementioned test however is not usually available in most of the common biochemical tests, but only with EGA. Other helpful tests for this diagnose, but with limited utility, are urea (cut-off of 45 mg/dL), creatinine/urea ratio, pH, anion gap (27). PCR test utilization and leukocytes counting discriminating between bacterial and viral gastroenteritis are of no utility and with no evidence.

HEMORRHAGIC DIATHESIS

Presence of an haemorrhage is often related to trauma or identifiable lesions, dealt with in the following chapters. When the bleeding appears spontaneous, especially on skin or mucosa, and represents the main symptom, it brings up the suspect of a coagulopathy, congenital or acquired. A patient with a congenital clotting problem rarely comes without any medical history clearly addressing the condition and treatment: the only exception is the Von Willendrand disease of moderate gravity, due to its high frequency. Some acquired Coagulopathies instead are to be kept under maximum consideration for their gravity and need for urgent intervention (28, 29). Oral anticoagulant therapy is the most common haemorrhagic risk situation, but also other therapies based on new medicines emerge (30). Thrombocytopenia on immune basis, secondary to a heparin treatment or to a myelotoxic therapy, represents one of the most frequent cases. Petechiae do prevail, but there can also be consistent mucosa bleeding. Acute hepatic impairment has several and evident causes, but in some cases can start off with a prevalence of haemorrhagic symptoms, in particular referring to Amanita intoxication, acute hepatitis and paracetamol intoxication. The causes have to be sought in the lack of coagulation factors, especially those with short half life, like V and VII factors but not VIII factor: hence PT lengthening is prevailing rather than aPTT’s (31). Presence of inhibitor (acquired haemophilia) is generally associated with an acute form and without further symptoms, and also could have a rapid and fatal course. Hence it is a laboratory priority to be able to detect, or at least suspect the condition through the execution of a “mixing test”(32). Acute CID can be caused by different correlated pathologies, in particular a difficult pregnancy, haematic disorders, meningitis or sepsis, serious traumas. Meningococcal sepsis or acute leukaemia have also to be considered (33). From a diagnostic point of view, platelets counting, PT, aPTT and fibrinogen represent an optimum screening panel that can be followed up by “mixing test” (able to detect acquired inhibiting factors) and eventually D-dimer, antithrombin and C protein tests (Table 10). Different POCT instruments are available for coagulate tests to be carried out immediately on the patient.

There is no evidence of their effectiveness in A&E and sometimes they supply results that have to be carefully evaluated (34). Hence these tests are only carried out in those situations where a fully equipped laboratory cannot be reached in due times (C grade).

DEHYDRATION IN ADULT

Different pathologies can cause dehydration. In the A&E clinical practice the most common causes are: diuretics misuse, fever, vomit and diarrhoea, burns, diabetes impairment, heatstroke. Different clinical point scores have been proposed for the dehydrated patient evaluation, based mainly on mucosa and skin aspect. Only in acute dehydration (where a parenteral re-hydration is necessary) laboratory testing is required. It is thus recommended not to request any test in the eventuality of a mild or moderate dehydration (Table 11). Depending upon dehydration causes, we can classify it in hypotonic, isotonic or hypertonic, and therefore laboratory tests can be difficult to interpret. Literature evidences (35-37) allow some advice regarding the most appropriate laboratory tests for this diagnosis (C Grade)(Table 12). The urea and sodium (Na) tests are of particular importance in determining the dehydration level.

An excessive diuretic effect is well highlighted thanks to the presence of metabolic alkalosis with a basis surplus. Dehydration causes that often occur in A&E are listed on Table 13. A proposal for laboratory tests regarding this condition is included in Table 14 (C Grade).

DYSPNEA

Dyspnoea is referred to as breathing difficulty. Because of its subjectivity it is difficult to quantify, and only laboratory tests, in particular the arterial Ega, can assess its gravity (38). Led oximetry is frequently used, thanks to its use simplicity and immediacy, but alone it is not enough to evaluate the oxygen level. A confirmation arterial Ega has also to be carried out for every single patient in order to confirm the situation. In fact, individual differences, like horny fingertip thickness, skin pigmentation, scarce peripheral perfusion, can actually cause important evaluation mistakes. An interpreting simplification of the above can be found in Table 15. Further laboratory tests on the basis of the symptoms have to be chosen following Table 16. Peculiar dyspnoea laboratory tests have to be considered thoroughly.